The etiology of most cases of diffuse pulmonary interstitial fibrosis in man is unknown, but there is increasing evidence that immunologic mechanisms are important. We propose to create interstitial fibrosis in animals by repeated intra-tracheal injections of Micropolyspora faeni (M. faeni). This organism is responsible for Farmer's lung disease in man and has been shown to produce granulomatous interestitial and intra-alveolar disease in rabbits. It also induces positive skin tests, macrophage migration inhibition, lymphocyte proliferation, activated pulmonary macrophages and serum and bronchoalveolar wash antibodies in these animals. We will inject M. faeni intratracheally into rabbits and hamsters. We will inject M. faeni weekly; every 6 weeks; intravenously as well as intratracheally; M. faeni which has been sonicated; M. faeni and Concanavalin A; M. faeni intratracheally and histamine intravenously; and M. faeni into hamsters. These maneuvers are designed to overwhelm or bypass enhanced pulmonary defense mechanisms, expose animals to a large number of antigens, increase permeability of the lung to intratracheal antigen and use a species not subjected to endogenous pulmonary infections. We will assess the histologic response of these treatments using morphometric analysis as well as pulmonary collagen and elastin content. We will also measure skin tests, pulmonary macrophage migration inhibition, lymphocyte proliferation and the amount of serum and bronchoalveolar wash antibodies. We will then determine if interstitial fibrosis produced by the above regimes is progressive by allowing animals to survive 4 and 8 weeks after cessation of treatment. The creation of a model of interstitial fibrosis in animals using M. faeni will allow better understanding of the pathogenetic mechanisms important in human interstitial fibrosis.